At the conclusion of a session on neuropsychological processing in bipolar disorder at last summer's meeting in Edinburgh of the International Society for Bipolar Disorders, a member of the audience thanked the panel for publicizing the cognitive deficits associated with bipolar disorder. As an advocate for and an individual with bipolar affective disorder, the woman claimed that while mental health professionals are focused on treating mood symptoms, only rarely do they consider the impact of neuropsychological difficulties on patients' lives. Indeed, she firmly stated that her poor memory and difficulty in concentrating influenced her daily life more than the affective symptoms of the disorder. Although it is unclear how well this woman represented the larger community of persons with bipolar disorder, it is clear that the cognitive sequelae of bipolar disorder and their impact on psychosocial functioning are rarely considered when developing treatment plans.

There is growing evidence that individuals with bipolar affective disorder have cognitive impairments, even during periods of symptom remission. While these impairments are typically less pronounced than those found in other psychiatric (eg, schizophrenia) or neurological (eg, Alzheimer dementia) illnesses, reduced neuropsychological ability appears to significantly affect psychosocial functioning in patients with bipolar disorder. In this article, we review evidence for cognitive disruptions in bipolar disorder and examine the relationship between these impairments and clinical outcome. In addition, we discuss the appropriateness of neuropsychological treatment targets in bipolar disorder.

Cognitive impairment
Although it is unclear how common cognitive impairment is among individuals with bipolar disorder, a significant portion of patients complain of neuropsychological difficulties. Because formal neuropsychological deficits have been documented in asymptomatic patients who do not complain of cognitive difficulties, it is possible that neuropsychological impairments may be more widespread than clinical experience suggests.1 Indeed, we recently reported that 75% of asymptomatic patients scored more than one standard deviation below healthy controls on at least 4 cognitive measures,2 suggesting widespread, but relatively mild, neuropsychological dysfunction in patients with bipolar disorder.

However, neuropsychological functioning is not a unitary process and consists of multiple, partially dissociable cognitive domains (eg, attention, processing speed, working or declarative memory, executive processing, language, intelligence quotient [IQ]). Currently, there is very little evidence of language or IQ deficits in patients with bipolar disorder. Rather, those euthymic patients with bipolar disorder who have cognitive difficulties tend to have attentional, executive, and declarative or long-term memory impairments.3

Neuropsychological impairments found in euthymic patients with bipolar disorder may be confounded by clinical variables such as the manifestation of subclinical symptoms or broader epiphenomena of an individual's illness history (eg, illness duration, number of hospitalizations, or medication use). While the importance of subclinical symptoms or illness sequelae is debated in the literature, a pragmatic approach suggests that since most patients who are in remission continue to have low-level cognitive symptoms, cognitive deficits should be considered when planning treatment strategies.

Effects of psychotropic medications on cognition
Although the use of psychotropic medications may affect neuropsychological functioning, systematic investigation of the cognitive impact of these agents in patients with bipolar disorder has been limited. A qualitative review concluded that while lithium had a negative effect on memory and speed of information processing, patients were often unaware of these deficits.4 Engelsmann and coworkers5 found that mean memory test scores remained stable over a 6-year interval in patients with bipolar disorder treated with lithium. Furthermore, after controlling for age and initial memory scores, there were no significant differences between patients with short- versus long-term lithium treatment on any measure. This suggests that long-term lithium usage is unlikely to cause progressive cognitive decline.5 Some antidepressant medications have been shown to have adverse cognitive effects, particularly those with anticholinergic properties.6

While few studies have examined neurocognitive performance in patients with bipolar disorder who were not medicated, we previously found comparably impaired verbal memory in persons receiving psychotropic medication (n = 32) and those who were drug-free (n = 17).7 Taken together, these findings suggest that cognitive deficits and underlying abnormalities in neuronal activation in patients with bipolar disorder are not primarily attributable to the use of psychotropic medications. However, large-scale, longitudinal investigations of patients with bipolar disorder on different medication regimens are necessary to fully address this question.